Freeze drying is used for both laboratory and production processes to preserve biological material. Freeze drying involves the application of heat to a frozen substance containing moisture so that the moisture is removed by sublimation without any other appreciable change in the substance. The reader is no doubt familiar with freeze dried instant coffee, prepared by freezing and drying brewed coffee. In a similar fashion, freeze drying preserves microbial serum for storage and distribution. Whole biological specimens or tissue samples also retain their original physical appearance after freeze drying. The absence of water in freeze dried specimens allows safe storage and display at normal room temperature.
The key to the retention of the physical characteristics of the freeze dried material lies in the fact that neither the freezing nor the sublimation process disturbs the physical orientation of the solid components of the material. Since the solid components are locked in an ice matrix during drying, they do not react chemically or change physically.
For moisture to be efficiently removed by sublimation, however, an optimum temperature and vapor pressure difference must be established and maintained between the frozen material and its atmospheric environment during the sublimation process. In a freeze dryer this state of unbalance is established by placing the frozen material in a vacuum chamber connected to a pump for maintaining a relatively low atmospheric pressure in the chamber, a low temperature condenser for further reducing the water vapor pressure in the chamber, and a heating system for applying heat to the frozen product to replace the heat of sublimation and thereby maintain a relatively fast rate of sublimation. The rate of sublimation, however, is limited by the maximum amount of heat which can be applied to the frozen material without causing thawing or "melt back" to occur. Melt back may occur even though the chamber pressure is low since the material dries at a defined surface within the material called the ice interface. As the ice interface moves deeper into the material, the dry material outside of the ice interface impedes the release of sublimated vapor thereby raising the temperature and relative pressure of the frozen material.
To avoid melt back, the rate of heat energy applied to the frozen material must not exceed the rate at which heat is absorbed by the release of sublimated vapor. Another limitation on the rate of sublimation is the rate at which the low temperature condenser can efficiently remove sublimated vapor due to icing and frosting of the condenser surfaces, and the rate at which sublimated vapor nigrates to the condenser. The presence of an effective low temperature condenser greatly reduces and simplifies the vacuum pumping requirement.
In practice, the freeze dryer must provide an active condensing surface lower than -40.degree. C., evacuation of the drying chamber to an absolute pressure of between 5 and 20 microns of Hg, and a controlled source of heat to the frozen material. The source of heat is controlled according to a time-temperature program responsive to a temperature sensor in the drying chamber, or preferably, by a sample probe in contact with the material being dried. For very sensitive materials, a system that can alternately apply both heat and refrigeration may be required. In order to dry a wide variety of products, the range of temperature control should be at least between -40.degree. and 65.degree..
Further background information on general freeze drying applications is found in Freeze Drying and Advance Food Technology, edited by S. A. Goldbith, L. Reynold, W. W. Rothmayr, Academic Press 1975; Advances in Freeze-drying, edited by L. Rey, Hermann, 115 Boulevard Saint-Germain, Paris VI, 1966; Freeze Drying of Foods, C. Judson King, CRC Press 1971; and Biological Application of Freezing and Drying, edited by R. J. C. Harris, Academic Press, 1954.
One particular application when precise temperature control is especially important is the freeze drying of production lots of pharmaceutical, biological and chemical products. For this purpose vacuum drying chambers up to six feet in diameter are provided for holding tens of thousands of serum bottles in a single run. The freeze drying pcoess is programmed according to a cooling and heating sequence of predefined temperatures at predefined times throughout the run. The program is typically stored in the memory of a microprocessor which also reads a product shelf temperature sensor, product temperature sensors, product resistance sensors, and the chamber pressure. From the stored sequence a microprocessor control program determines the desired temperature throughout the cycle and checks that the product temperature for solidification is obtained after cooling and that proper vacuum is obtained at the beginning of the drying sequence. The control program further checks the product temperature and resistance during drying and, if necessary, prolongs the drying sequence.
The microprocessor control passes the desired parameter to a shelf temperature control system which maintains the product shelf at the desired temperature. In the conventional production dryer, a refrigerator is activated to lower the temperature of a heat transfer fluid when the product shelf temperature exceeds the desired temperature, and the heater is energized to warm the heat transfer fluid when the product shelf temperature falls below the desired temperature. Circulation of the heat transfer fluid through the shelf assembly, heater, and a heat exchanger cooled by the refrigerator is provided by a centrifugal pump.